Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila

Elife. 2018 Apr 16;7:e29988. doi: 10.7554/eLife.29988.


Imaginal progenitors in Drosophila are known to arrest in G2 during larval stages and proliferate thereafter. Here we investigate the mechanism and implications of G2 arrest in progenitors of the adult thoracic tracheal epithelium (tracheoblasts). We report that tracheoblasts pause in G2 for ~48-56 h and grow in size over this period. Surprisingly, tracheoblasts arrested in G2 express drivers of G2-M like Cdc25/String (Stg). We find that mechanisms that prevent G2-M are also in place in this interval. Tracheoblasts activate Checkpoint Kinase 1/Grapes (Chk1/Grp) in an ATR/mei-41-dependent manner. Loss of ATR/Chk1 led to precocious mitotic entry ~24-32 h earlier. These divisions were apparently normal as there was no evidence of increased DNA damage or cell death. However, induction of precocious mitoses impaired growth of tracheoblasts and the tracheae they comprise. We propose that ATR/Chk1 negatively regulate G2-M in developing tracheoblasts and that G2 arrest facilitates cellular and hypertrophic organ growth.

Keywords: ATR/mei-41; Chk1/Grapes; D. melanogaster; G2 arrest; Tracheoblasts; cellular growth; developmental biology; hypertrophic growth; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • Checkpoint Kinase 1 / metabolism*
  • Drosophila
  • Drosophila Proteins / metabolism*
  • G2 Phase Cell Cycle Checkpoints*
  • Hypertrophy*
  • Metamorphosis, Biological*
  • Protein Serine-Threonine Kinases / metabolism*
  • Stem Cells / physiology*
  • Trachea / growth & development*


  • Cell Cycle Proteins
  • Drosophila Proteins
  • Checkpoint Kinase 1
  • Mei-41 protein, Drosophila
  • Protein Serine-Threonine Kinases
  • grp protein, Drosophila

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.